title: Bacterial infection increases periodontal bone loss in diabetic rats through enhanced apoptosis.
abstract: Periodontal disease is the most common osteolytic disease in humans and is significantly increased by diabetes mellitus. We tested the hypothesis that bacterial infection induces bone loss in diabetic animals through a mechanism that involves enhanced apoptosis. Type II diabetic rats were inoculated with Aggregatibacter actinomycetemcomitans and treated with a caspase-3 inhibitor, ZDEVD-FMK, or vehicle alone. Apoptotic cells were measured with TUNEL; osteoblasts and bone area were measured in H&E sections. New bone formation was assessed by labeling with fluorescent dyes and by osteocalcin mRNA levels. Osteoclast number, eroded bone surface, and new bone formation were measured by tartrate-resistant acid phosphatase staining. Immunohistochemistry was performed with an antibody against tumor necrosis factor-α. Bacterial infection doubled the number of tumor necrosis factor-α-expressing cells and increased apoptotic cells adjacent to bone 10-fold (P < 0.05). Treatment with caspase inhibitor blocked apoptosis, increased the number of osteoclasts, and eroded bone surface (P < 0.05); yet, inhibition of apoptosis resulted in significantly greater net bone area because of an increase in new bone formation, osteoblast numbers, and an increase in bone coupling. Thus, bacterial infection in diabetic rats stimulates periodontitis, in part through enhanced apoptosis of osteoblastic cells that reduces osseous coupling through a caspase-3-dependent mechanism.
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pacios
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Research and Health Promotion, School of Dental Medicine, University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: Oelisoa
authors.initials: O
authors.lastname: Andriankaja
authors.affiliation: Department of Periodontology, School and Hospital of Stomatology, Peking University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Maher
authors.initials: M
authors.lastname: Alnammary
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jason
authors.initials: J
authors.lastname: Bae
authors.affiliation: Prosthodontics and Periodontics Department, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Brito Bezerra
authors.affiliation: Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey.
authors.forename: Helen
authors.initials: H
authors.lastname: Schreiner
authors.affiliation: Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fine
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: dtgraves@dental.upenn.edu.
authors.forename: Dana T
authors.initials: DT
authors.lastname: Graves
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans; D016301:Alveolar Bone Loss / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D048909:Diabetes Complications / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D016871:Pasteurellaceae Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D010518:Periodontitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha